- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Jackson-Jones, K. A., Simons, L. M., Huang, S., Joseph, T., Sawyer, A., Wu, L., Hultquist, J. F.N6-methyladenosine (m6A) iis the most prevalent internal modification of cellular and viral RNA and is critical 32 to the regulation of its localization, stability, and translation. Previous studies on the role of m6A during HIV-1 replication have produced conflicting results. Since m6A function can vary dramatically by cell type and state, here we aimed to clarify the role of the m6A machinery during HIV-1 replication in primary CD4+ T cells. Using CRISPR-Cas9 we targeted 46 genes implicated in m6A or […]
- by Lin, Y., Liou, B., Fannin, V., Adler, S., Mayhew, C. N., Hammonds, J. E., Hu, Y.-C., Tchieu, J., Zhang, W., Zhao, X., Beres, R. L., Setchell, K. D., Kaynak, A., Qi, X., Feldman, R. A., Sun, Y.Neuronopathic Gaucher disease (nGD) is a lysosomal storage disorder caused by GBA1 mutations, leading to defective acid {beta}-glucosidase (GCase) and accumulation of glycosphingolipid substrates, causing inflammation and neurodegeneration. Patients with nGD manifests severe neurological symptoms, but current animal models fail to fully recapitulate human condition, posing a major barrier to the development of effective therapies targeting the brain. To bridge this gap, we have developed midbrain-like organoids (MLOs) from human induced pluripotent stem cells (hiPSCs) of nGD patients with GBA1L444P/P415R […]
- by Bandehagh, A., Taylor, N. L.Plants maintain energy balance under salinity stress through increased respiration and energy use, processes also associated with reactive oxygen species generation. Although respiration imposes a high energy cost, mitochondrial respiration and the tricarboxylic acid (TCA) cycle activity are vital for ATP production and providing electron donors that drive ion exclusion and ROS detoxification. This study examined the molecular basis of respiratory responses to salinity in barley using physiological, biochemical, metabolomic, and proteomic analyses. Salt exposure resulted in sodium accumulation, decreased […]
- by Dillon, S., Clews, C., Kurian, D., Nudelman, F., Farquharson, C., Stephen, L. A.Matrix Vesicles are a crucial step in producing a mineralised, healthy skeleton. Released from chondrocytes and osteoblasts, they concentrate calcium and phosphate to establish the deposition of hydroxyapatite around and within the collagen fibrils of the extracellular matrix, becoming embedded in the matrix in the process. In the 55 years since H. Clarke Anderson first described them, blebbing from the surface of chondrocytes, a consensus on their role, contents and their biogenesis, has yet to be reached. This is in […]
- by Reusch, L., Mathew, N. R., Schön, K., Kosik, I., Gibbs, J. S., Mankowski, M. C., Besavilla, D. F., yewdell, j., Bemark, M., Angeletti, D.Antigenic drift in influenza A virus hemagglutinin (HA) limits humoral protective immunity. Here, we combine cell fate mapping with adoptive transfer of antigenic-site-specific antibodies (Abs) and memory B cells (MBCs) with moderately drifted HA vaccination in mice to better understand how this influences immune escape and protective responses. We demonstrate that drift in vaccine antigens affects MBC reactivation and naive B cell responses in germinal centers (GC). Strikingly, passively transferred monoclonal and polyclonal Abs suppress cognate epitope-specific GC B cell […]
- by Arcario, M. J., Wu-Chen, E. J., Henin, J., Brannigan, G., Cheng, W. W.-L.Open-channel structures have been determined of multiple pentameric ligand-gated ion channels (pLGIC), including the prokaryotic model pLGIC, ELIC (Erwinia ligand-gated ion channel). For many of these structures, it remains uncertain whether they represent the physiologic open-channel state because the conditions used for structure determination do not match those of functional measurements in cell membranes. Here, molecular dynamics (MD) simulation is used to examine the ion conduction properties of the ELIC open-channel structure, which was determined using a non-desensitizing mutant called […]
- by Patel, A., Zhong, X., Moffett, M. A., Sun, Y., Dennis, A. M.Significance: While shortwave infrared (SWIR) imaging provides superior tissue penetration and reduced autofluorescence for preclinical applications, quantitative fluorescence analysis is hindered by the limited dynamic range of InGaAs cameras, forcing a focus on either bright or dim anatomical features. Aim: We develop a high dynamic range (HDR) imaging method specifically adapted for the high-noise characteristics of InGaAs detectors to enable quantitative fluorescence imaging across wide intensity ranges. We demonstrate that one-time camera calibration based on a series of images encompassing […]
- by Han, J.-R., Li, S., Lian, W.-H., Xu, L., Duan, L., Li, J., Shi, G.-Y., Wei, Q.-C., Ali, M., Li, W.-J., Dong, L.The genus Micromonospora, a key member of the actinomycetes, has demonstrated considerable potential for natural product biosynthesis. In this study, we isolated 15 Micromonospora spp. strains from desert soil and marine sediment samples, eight of which represent four novel species. To explore the biosynthetic capacity of this genus, we performed an integrated analysis of Micromonospora reference genomes. Pan-genomic analysis further unveiled the core biosynthetic characteristics of the genus responsible for producing terpenes and polyketides. Further multi-omics investigation, combining genomic and […]
- by Tan, J., Xu, Y., Tian, L., Chen, X., Fischer, M., Zhang, Y., Li, X.Neurospora crassa has long served as a key fungal genetics model, facilitating discoveries like the ''one gene, one enzyme'' hypothesis. It produces many conidia, mostly with two or three nuclei and each nucleus was once thought to contain a full haploid genome. Using flow cytometry and FISH, we found that N. crassa haploid chromosomes are divided among nuclei, each conidium is haploid – challenging the ''one nucleus, one whole genome'' rule.
- by Steele, M. I., Oxender, E. E., Ge, C., Queller, D. C., Strassmann, J. E.In bacteria, defense against predators and competitors often requires cooperation within large clonal bacterial populations. Mutations that inactivate biosynthesis of costly molecules involved in cooperative defense can increase the growth rate of the mutants, while mutant cells continue to benefit from the efforts of wild type cells. The GacA-GacS signaling pathway regulates biosynthesis and secretion of toxic secondary metabolites and proteins that play crucial roles in bacterial defense in Pseudomonas species, including resistance to the protozoan predator Dictyostelium discoideum. A […]
- by Pandey, S., Abu, Y. F., Singh, P. K., Roy, S.Prenatal opioid exposure disrupts gut homeostasis and causes gastrointestinal complications in offspring, but the mechanisms remain unclear. Here using a murine model of prenatal hydromorphone exposure, we examined gut microbiota, intestinal injury, transcriptomic signatures, and chromatin accessibility. Exposed pups displayed marked dysbiosis, epithelial damage, and upregulation of inflammatory gene programs accompanied by relaxed ileal chromatin. Cross-fostering to opioid-naive dams restored microbial diversity, reestablished metabolite-producing taxa, and reversed injury-associated transcriptional and chromatin changes. Fecal microbiota transplantation from exposed dams recapitulated intestinal […]
- by Rinta-Harri, K., Koponen, T., Mojzita, D., Jouhten, P., Liti, G., Krogerus, K.Hybrid vigor, or heterosis, is widely exploited in yeast strain improvement. Yet, how ploidy and genetic background jointly shape heterosis across industrially relevant stresses remains unclear. Here, we generated 1023 Saccharomyces cerevisiae intraspecific hybrids derived from 18 genetically diverse parents, yielding sets of hybrids with variable ploidy for the same parental combinations. High-throughput growth assays in media with five stress conditions (14% ethanol, 1.5 M NaCl, 0.15 M lactic acid, 0.05 M acetic acid, 0.05 M HMF) revealed extensive heterosis […]
- by Aguirre-Sourrouille, Z., Hackl, T., Oksanen, H. M., Quax, T. E. F.The ongoing evolutionary arm race between archaea and their viruses has led to the development of diverse defense systems against viruses. While recent computational approaches have uncovered many bacterial antiviral defense systems, the viral infection strategies and antiviral responses of archaea remain poorly explored. In this study, we identified antiviral defense systems encoded in the genomes of 20 recently sequenced haloarchaeal strains. These systems are representative of the broader repertoire of defense systems present across all 253 complete sequenced Halobacteria […]
- by Mahmud, M. R., Orro, T., Munsterhjelm, C., Pessa-Morikawa, T., Ahlqvist, K., Junnikkala, S., Konig, E., Pujolassos, M., Calle, M. L., Kwon, H. N., Oliviero, C., Heinonen, M., Niku, M.Maternal microbiota modulates the development of the microbiota in the o[ff]spring. E[ff]ects of gestational antibiotics are not well understood, as most studies have focused on the perinatal period. We treated sows with penicillin, tetracycline or saline on days 78-80 of the 114-119-day gestation, a critical period in the fetal immune system development. Microbiotas were analyzed by 16S rRNA gene amplicon sequencing in sow feces and vagina at days 77 and 113, in colostrum, and in piglet feces at three days, […]
- by Balouz, V., Lopez, R., Conte, N., Abal, M., Ducrey, I., Giorgi, M. E., de Lederkremer, R. M., Altcheh, J., Ciocchini, A. E., Melli, L. J., Marino, C., Buscaglia, C. A.Background: Chagas disease (ChD), caused by the parasitic protozoan Trypanosoma cruzi, is a lifelong, neglected tropical disease with substantial medical and socioeconomic impact. Despite this situation, currently available diagnostic and therapeutic methods display serious limitations. A promising strategy to improve ChD serodiagnosis involves targeting parasite carbohydrate antigens, particularly the -galactosyl-rich mucins that coat the surface of bloodstream trypomastigotes (tGPI-mucins). Methods/Principle Findings: Here, we present a concise and efficient protocol for the chemical synthesis of a tGPI-mucin-derived glycotope, the disaccharide -d-Galp-(1[->]3)-{beta}-d-Galp, […]
- Functional Effects of CD33 SNP rs12459419 on Microglial Gene Regulation and Alzheimer's Disease Riskby Lu, Y.The SNP rs12459419 in exon 2 of the CD33 gene alters mRNA splicing, influencing the expression of a truncated isoform lacking the IgV domain. This isoform enhances amyloid-beta clearance by microglia and is associated with a reduced risk of Alzheimer's disease (AD). In this study, we integrate transcriptomic, genomic, epigenomic, and population genetics data to test the hypothesis that rs12459419 regulates CD33 expression in a genotype-dependent manner. We leveraged public datasets including GTEx, 1000 Genomes, ENCODE, and UCSC Genome Browser. […]
- by Laihonen, L., Tomberg, T., Vuorijoki, L., Mulo, P., Rantala, M.Ongoing climate change has intensified heatwaves, which suppress photosynthesis and thus threatens agriculture. While acute heat stress damages photosystem II (PSII), detach light harvesting complex (LHC)II from PSII core and linearize thylakoid membrane, the consequences of prolonged recurring moderate heat exposure across the plant life cycle remain unclear. Here we characterized the effects of long-term daily exposure to high temperature on thylakoid membrane ultrastructure, photosynthetic protein complexes and their function, as well as to the redox states of PSI electron […]
- by Courtney, S. J., Gallichotte, E., Nilsson, E., Trammell, C., Kimball, K., Fagre, A., Vilander, A., Overby, A. K., Ebel, G. D.Powassan virus (POWV) is an emerging tick-borne flavivirus that causes disease in humans. POWV has considerable genetic and phenotypic diversity, including highly variable replication in vitro and pathogenesis in mice. This study sought to define the extent of variability in pathogenesis within POWV lineage II in mice and investigate possible viral determinants. Relative to other strains, two New York-derived isolates, NY.19.12 and NY.19.32, caused earlier clinical signs and earlier detection of viral RNA (vRNA) in the spleen and brain compared […]
- Multi-Dimensional Spatiotemporal Attention Neural Network for Next Generation Sequencing Basecallingby Peng, K., Chen, W., Yao, T., Xia, H., Fu, G., Li, G., Bao, Y., Liu, E., Zhao, L., Wang, G.Next-generation sequencing (NGS) remains the most used sequencing technique in the field of genomics. Traditional basecall methods face significant challenges in decoding high density sequencing data due to inherent noise in biochemical reactions and limitations of instruments. Here, we present a multi-dimensional deep learning neural network based on spatiotemporal attention mechanism named AICall. The network skips computationally heavy but less effective steps of peak finding and brightness extraction/correction, and directly basecalls from the time sequence of multi-dimensional image stacks obtained […]
- by Mallecot, E., Berti, V., Petitjean, M., MEYER, J., Gueye, S., Morel-Journel, T., Clermont, O., Poirel, L., Denamur, E., Royer, G., Armand, L.Cefiderocol (FDC) is a new siderophore-conjugated cephalosporin that enters the periplasm via iron transport systems. However, the specific contribution of individual iron uptake pathways to FDC activity remains unclear. We investigated the role of 12 iron acquisition systems using several Escherichia coli strain collections. FDC MICs were determined in iron-depleted and iron-supplemented media for E. coli mutants (Keio and pathogenic island [PAI]-deleted collections) and for clinical wild-type or TEM-producing E. coli (WT/TEM-Ec) and NDM-producing (NDM-Ec) isolates. The distribution of iron […]